Scientists have provided new evidence that using
more fish oil than vegetable oil in the diet decreases the formation
of chemicals called prostanoids, which, when produced in excess,
increase inflammation in various tissues and organs. The results,
by William L. Smith, Professor and Chair of Biological Chemistry
at the University of Michigan, Ann Arbor, and colleagues, may
help in designing new anti-inflammatory drugs with fewer side
effects than the ones currently available.

"Prostanoids help control blood pressure, fight allergies,
and modulate inflammation, but too much of them -- especially
those made from vegetable oils -- can also lead to increased pain,
swelling, and redness in various tissues," Smith says. "Our
study shows that prostanoids made from fish oil are less effective
at causing pain and swelling than those made from vegetable oil
and that adding fish oil to the diet decreases the amount of prostanoids
made from vegetable oil."

Smith and colleagues looked at the mutual effects of both oils
by changing their respective amounts in cultured cells. As expected,
a relative increase in fish oil lowered the amount of prostanoids
from vegetable oil, although not always in the expected proportions.

Both fish and vegetable oils are converted into prostanoids
through chemical reactions that are aided by enzymes called
cyclo-oxygenases (COX), two types of which -- COX-1 and COX-2
-- are involved in the reactions. The scientists showed that,
in reactions involving COX-1, when more fish oil is present,
it preferentially binds to COX-1, thus limiting vegetable oil's
access to this enzyme. But in reactions involving COX-2, increasing
the amount of fish oil did not change the way it binds to COX-2,
so a significant portion of vegetable oil was still converted
to prostanoids.

"This was completely unexpected," Smith says. "This
new result shows that COX-2 does not 'prefer' fish oil to vegetable
oil. Regardless of the amount of extra fish oil that we added,
COX-2 still helped convert all the vegetable oil available."

This finding reveals for the first time a limit to how the
body naturally regulates levels of prostanoids produced by fish
and vegetable oil. If both oil types are present in the body,
levels of prostanoids from fish oil will, in general, be higher
than those coming from vegetable oil, but mechanisms such as
the one involving COX-2 can counter this trend.

The researchers are now investigating why COX-1 and COX-2 act
differently. One possibility is that since COX-2 has two binding
sites, it can bind to both fish and vegetable oils. When fish
oil binds to one of the two sites, it may prepare the other
site to bind more easily to vegetable oil, a process called
allostery.

Smith and his colleagues hope that by further investigating
how prostanoids are regulated in the body, they can design potential
drugs that bind to COX-2 and decrease levels of the vegetable
oil prostanoids.

"The drugs that are currently used to inhibit COX-1 and
COX-2 provide relief from the symptoms of inflammation and pain,
but they still have many side effects," Smith says. "By
better understanding how prostanoids work at the cellular level,
we hope to find new ways to regulate inflammation and create
better anti-inflammatory drugs."

The new study is to be published in the August 3 issue of the
Journal of Biological Chemistry.